An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury

详细信息    查看全文

• 作者：Jacek M. Kwiecien^a ; ^b ; ^{kwiecien@mcmaster.ca" class="auth_mail" title="E-mail the corresponding author} ; Bozena Jarosz^b ; ^{bozenajarosz@poczta.onet.pl" class="auth_mail" title="E-mail the corresponding author} ; Wendy Oakden^c ; ^{wendy.oakden@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Michal Klapec^d ; ^{michalklapec@op.pl" class="auth_mail" title="E-mail the corresponding author} ; Greg J. Stanisz^b ; ^c ; ^{stanisz@sri.utoronto.ca" class="auth_mail" title="E-mail the corresponding author} ; Kathleen H. Delaney^a ; Edyta Kotlinska-Hasiec^e ; ^{kedith@poczta.onet.pl" class="auth_mail" title="E-mail the corresponding author} ; Rafal Janik^c ; ^{raf.janik@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Radoslaw Rola^b ; ^{rola.radoslaw@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Wojciech Dabrowski^e ; ^{w.dabrowski5@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Spinal cord injury ; Phagocytosis of myelin debris ; Cavity of CNS injury ; Subdural infusion ; Inhibition of secondary inflammation
• 刊名：Neurologia i Neurochirurgia Polska
• 出版年：2016
• 出版时间：January-February 2016
• 年：2016
• 卷：50
• 期：1
• 页码：7-15
• 全文大小：4312 K

文摘

Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4 mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125–2.0 mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125–2.0 mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process.